Artikel
Subnormothermic machine perfusion with hemoglobin-based oxygen carriers for tissue preservation in vascularized composite allotransplantation
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Autoren
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Riccardo Schweizer
- Department of Plastic Surgery and Hand Surgery, UniversityHospital Zurich, University Zurich, Switzerland; Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA
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Sinan Oksuz
- Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Department of Plastic, Reconstructive and Aesthetic Surgery, Gulhane Military Medical Academy, Turkey
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Chiaki Komatsu
- Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA
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Vijay S. Gorantla
- Department of Plastic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA
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Paulo Fontes
- McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA; Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, USA
| Veröffentlicht: | 28. September 2015 |
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Gliederung
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Background: Vascularized composite allotransplantation such as hand/face transplantation is a clinical reality. Ischemia-reperfusion injuries (IRI) of vertical rectus abdominis muscle (VRAM) allografts were assessed in a preclinical large animal model comparing cold static preservation (CSP) with machine perfusion (MP) using a new cell-free hemoglobin-based oxygen carrier (HBOC) solution.
Methods: Pig VRAM allografts were procured and transplanted heterotopically (cervical) to recipients after 14h cold ischemia time (CIT). Controls (n=4) underwent CSP, the study group (n=4) underwent MP/HBOC (21°C). The MP perfusate was assessed for arterial blood gases (pH, pO2, pCO2, BE, HCO3, lactate). Both groups had their allografts weighted before/after preservation. All recipients received triple-immunosuppression (Tacrolimus/MPA/Prednisone) for 7d. Initial clinical and histopathological analysis was conducted. Subsequent studies included transcriptomics, proteomics and metabolomics.
Results: MP allografts were perfused at low pressures (55 mmHg), low flows (20-80 ml/min) and full oxygenation (FiO2=60% @ 400ml/min) over 14h. The allografts perfused well and showed no signs of tissue edema or weight gain after MP. Lactate levels were kept under 4 after 14h of MP. The pH was kept within physiologic range without the use of NaHCO3 infusions during MP. There were no signs of tissue damage over 14h of MP in H&E and TUNEL stainings. There was a significantly lower amount of muscle fiber disruption and necrosis in the MP group compared to CSP flaps after transplantation. TUNEL staining showed a lower amount of apoptotic bodies in the MP group. Myoglobin blood levels were significantly higher at day 1 in the CSP group.
Conclusion: MP/HBOC provides effective oxygenation for VRAM allografts over an extended period (14h) with no signs of endothelial cell damage/tissue edema. MP minimizes IRI when compared to CSP. Myoglobin release and histopathological damage were more pronounced after CSP.
